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Angewandte Chemie International Edition 2018-04-14

Natural Product Diversification Mediated by Alternative Transcriptional Starting

Nicholas J. Tobias; Annabell Linck; Helge B. Bode

文献索引:10.1002/anie.201713199

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摘要

10.1002/anie.201713199图片

Photorhabdus luminescens dedicates a significant proportion of its genome to the production of natural products. These products and the structural variation in their derivatives may occur by a number of well‐described mechanisms, such as module skipping or precursor promiscuity. Cappable‐seq was used to identify transcriptional start sites of many of the gene clusters present in P. luminescens TTO1. We discovered that variations associated with the non‐ribosomal peptide synthetase Kol, which is responsible for kolossin A production, possessed a number of internal transcripts that lead to synthesis of the smaller kolossin derivatives kolossin B and C. The data here support a new mechanism of natural product biosynthetic variation whereby mRNA may code for shorter NRPS enzymes in addition to full‐length proteins, resulting in the production of smaller peptide derivatives.